A high-performance liquid chromatographic method for screening angiotensin II receptor antagonists in human urine

A high-performance liquid chromatographic method with photometric detection has been developed for the determination of five angiotensin II receptor antagonists (ARA II): Losartan, Irbesartan, Valsartan, and Candesartan cilexetil and its metabolite Candesartan M1. Reversed-phase chromatography was performed at room temperature on a mu Bondapak C-18 column; compounds were separated by gradient elution with mixtures of acetonitrile and 0.1 M acetate buffer, pH 4, at different flow rates. Detection was at 254 nm. Urine samples were purified by solid-phase extraction on C-8 cartridges, a procedure enabling recoveries > 85% for all the drugs except Candesartan cilexetil (71%). The analysis time was less than 50 min, including extraction (chromatographic analysis lasted 25 min). Intra- and inter-day coefficients of variation for all the compounds were below 8% and the method was highly accurate (relative error, RE, usually ca 3%). The accuracy precision, and sensitivity (limit of quantitation 0.4 mug mL(-1)) of the method were sufficient for application to the screening of these ARA II in spiked urine samples.